Dietary chitosan alleviates Enterohemorrhagic Escherichia coli induced intestinal injury by reducing bacterial colonization and restoring mucosal immune homeostasis in weaned piglets.

Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is a notable zoonotic enteric pathogen that is well recognized for causing severe intestinal disease in humans. However, its effects on intestinal barrier integrity and mucosal immune homeostasis in weaned piglets remain insufficiently characterized. Whether higher-molecular-weight chitosan (HMWC) can mitigate these alterations also remains unclear. This study investigated the protective effects of dietary HMWC against EHEC-induced intestinal injury in weaned piglets. 108 piglets were randomly allocated to three groups: control (CON), EHEC challenge (ECON), and EHEC challenge with 100 mg/kg HMWC supplementation (ECOS). Piglets in the challenged groups were orally gavaged with 100 mL of LB broth containing 1 × 109 CFU/mL EHEC on day 6, and the experiment lasted 21 d. EHEC challenge impaired fecal consistency and feed:gain ratio (F:G), increased fecal shedding of total E. coli and EHEC, elevated neutrophil counts, and aggravated jejunal epithelial apoptosis. Moreover, it also impaired intestinal barrier integrity, as indicated by increased serum diamine oxidase, reduced jejunal ZO-1 expression, and decreased abundance of sIgA-positive cells in the jejunal epithelium, while disturbing mucosal immune homeostasis, as shown by altered macrophage polarization, disrupted lymphoid T-cell subsets, and dysregulated immune-related gene expression. However, dietary HMWC attenuated these adverse effects, as reflected by a tendency toward reduced fecal bacterial shedding, attenuated epithelial apoptosis, preserved barrier integrity, suppressed M1-associated macrophage polarization, and partially restoring mucosal immune homeostasis. These findings indicate that dietary HMWC alleviates EHEC-induced intestinal dysfunction, possibly in association with reduced fecal bacterial shedding and improved mucosal immune regulation.